1. Field of the Invention
This invention relates to apparatus for laboratory specimen preparation, and in particular to such apparatus which operates automatically to process specimens in preparation for a plurality of physical chemical or biological tests, for quality control, etc. This apparatus will operate equally well in terrestrial or space (microgravity) environments. The apparatus comprises a multi-compartmented specimen preparation unit with force-sensitive valves and a centrifugal processing unit with means for locally rotating the former unit into any desired orientation with respect to the centrifugal force vector, about either of two axes.
2. Information Disclosure Statement
Currently, the standard mode for conducting tests on specimens such as human blood samples requires that these specimens be partially or wholly prepared by technicians in accordance with predetermined procedures by measuring aliquots, adding diluents, reagents, etc. It is often necessary to permit a specimen to incubate for a predetermined time and to be filtered as well as centrifuged. The number of individual steps necessary in order to prepare a particular specimen for testing can be large and the steps themselves can be complex and require special skills. Normally, a technician performs these steps in a laboratory setting. This procedure can take substantial time and is subject to human error.
It would, therefore, be beneficial to be able to prepare a specimen for testing without human intervention. To date, no single apparatus is known which can accurately and reliably process specimens in preparation for the multitude of testing procedures which are currently available, that can adapt to a wide panel of future testing procedures, and also operates independently of gravity. This independence is achieved by using centrifugal force to induce fluid flow in a particular direction within a freely orientable specimen processing unit.
Schultz, et al., Clin. Chem. 31(9): 1547 (1985) describe a system in which a multichambered test pack containing liquid reagents is subjected to alternating centrifugal fields, oriented at right angles to each other. The primary rotation is that of the centrifuge rotor, which causes the test pack to orbit the rotor axis. The test pack, which is essentially planar, lies in the plane of rotation of the rotor, and may be rotated secondarily about its own axis, perpendicular to the main face of the test pack and parallel to the rotor axis.
While it is thus possible to change the relative g-force vector within the test pack, there is no provision for rotating the test pack out of the plane of rotation of the rotor. If the test pack had a plurality of "vertical" (parallel to rotor axis) layers of compartments, it would not be possible to centrifugally transfer fluid between layers. In my device, each test pack may be rotated about two local axes as well as being revolved about the rotor axis.
Moreover, the test pack taught by Schultz is valveless. Thus, fluid may leak from one layer to another under gravitational influence. My test pack is equipped with force-sensitive valves, which will not be opened by gravitational forces alone.
Belman, U.S. Pat. No. 3,882,716 describes a centrifugal apparatus having centrifuge cells mounted at a fixed, acute angle to the drive shaft, each of these cells being rotatable about its own axis. This "satellite" rotation is intended to agitate the contents of the cell. At the lower end of each cell is a cuvette. Means are provided for bringing each cuvette into registry, sequentially, with a single read-out instrument. While the orbital position of the cells is controlled, no control is exercised over the rotational position of each cell and thereby over the local centrifugal force vector. Moreover, the cells have only one rotational degree of freedom.
Proni, U.S. Pat. No. 3,768,727 discloses another centrifugal analyzer in which sample columns are independently rotated about their own, fixed, substantially vertical axis.
Anderson, U.S. Pat. No. 3,586,484 describes a multistation analytical photometer. A central transfer disc initially holds precipitating solutions and sample solutions, separated by partitions. As the rotor spins, these solutions move to peripheral sedimentation chambers, and mix. When the rotor is returned to rest, supernatant drains into holding chambers. There is no provision for a specimen collecting and processing module which is separable from the rotor assembly, or for reorienting that module so that the centrifugal force applied by the rotor causes fluid to flow within the module in a different, non-coparallel direction. While the flow of supernatant in Anderson is in a direction perpendicular to the original flow of precipitant and sample, this second flow is induced by natural gravitational forces rather than by centrifugation. See also Klose, U.S. Pat. No. 4,557,600.
Guigan, U.S. Pat. No. 4,463,097 describes the use of centrifugal force to transfer sample from one compartment to another. These compartments are integral to the rotor assembly, and the compartments always receive the sample in the same sequence. The sample "zigzags" as it moves outward, the direction of rotation of the rotor being reversed at each step. The operability of the device is directly related to the special arrangement and connection of the compartments. See also Guigan, U.S. Pat. No. 4,519,981.
Curtis, U.S. Pat. No. 4,390,399 shows the combination of a test package with a spinning rotor for the purpose of chemical analysis. Pneumatically actuated barriers, flexible diaphragms, and rupturable seals are used to control and transport the sample from one compartment of the test package to the next in a programmed sequence. The direction of the centrifugal force with respect to the test package is constant throughout the sequence, that is, the rotor is used to induce flow in only one direction. The package has a fixed orientation with respect to the rotor.
Farina, U.S. Pat. No. 4,244,694 (FIG. 2) refers to a centrifugal analyzer in which test tubes are suspended by their rims in ball seats of the rotor assembly. When the rotor is spun, the test tubes swing out. There is no teaching, however, of using rotor speed to control the direction of flow of sample within the test tube.
Hardy, U.S. Pat. No. 4,092,113 places a blood sample device in the bucket of a conventional centrifuge. The bucket is swung out to a horizontal position when the rotor is start. The device comprises inner and outer sample vessels connected by a leakage path. There is no provision for reorienting the device so that the centrifugal force will induce fluid flow in another direction.
Aeschlimann, U.S. Pat. No. 4,236,666 describes a centrifuge with pivotable mounted magazines. This design is to facilitate positioning the magazines in either a slightly tilted "decanting" orientation or a generally horizontal "centrifuge" orientation.
Mochida, U.S. Pat. No. 4,479,720 discloses a rotor with a determinable angle of inclination, for increasing the rate of a reaction in tubes held by the rotor by increasing the contact area.
Sogi, U.S. Pat. No. 4,208,484 describes apparatus for automatically transferring a centrifuge tube to a centrifuge.
Anthon, U.S. Pat. No. 3,151,073 discloses a self-indexing centrifuge rotor.
DeGrave, U.S. Pat. No. 4,595,563 presents apparatus for sample transfer and analysis by centrifugation. Cuvette carriers are pivotably connected to the ends of the rotor arms. The apparatus is designed so that the inclination changes as the rotor speed is increased. Sample transfer takes place at one speed, and sample analysis at a higher speed.
Yamamoto, U.S. Pat. No. 4,632,808 relates to a chemical manipulator capable of automatically transporting a bucket between stations. The bucket may be moved in the x, y, or z directions. The manipulator is used to transfer the bucket to a centrifugal separator.
The disclosures of the above-identified patents are incorporated by reference.